Comparison of the Performance of a Novel, Smartphone-based, Head-mounted Perimeter (GearVision) With the Humphrey Field Analyzer.

PRECIS: The agreement between a head-mounted perimeter [GearVision (GV)] and Humphrey field analyzer (HFA) for total threshold sensitivity was a mean difference of -1.9 dB (95% limits of agreement -5 to 1). GV was the preferred perimeter in 68.2% of participants. PURPOSE: The purpose of this study was to compare reliability indices and threshold sensitivities obtained using a novel, smartphone-based, head-mounted perimeter (GV) with the HFA in normal, glaucoma suspect and glaucoma patients. A secondary objective was to evaluate the subjective experience participants had with both perimeters using a questionnaire. METHODS: In a prospective, cross-sectional study; 107 eyes (34 glaucoma, 18 glaucoma suspect, and 55 normal) of 54 participants underwent HFA and GV in random order. The main outcome measure was the agreement of threshold sensitivities using Bland and Altman analysis. Participants also completed a questionnaire about their experience with the devices. RESULTS: Median false-positive response rate for GV was 7% (4% to 12%), while for HFA it was 0% (0% to 6%, P<0.001). Median false-negative response rate was similar for both tests. In all, 84 eyes with reliable HFA and GV results were included in the final analysis. Median threshold sensitivity of all 52 points on HFA was 29.1 dB (26.5 to 30.7 dB) and for GV was 30.6 dB (29.1 to 32.6 dB; P<0.001). Mean difference (95% limits of agreement) in total threshold sensitivity between HFA and GV was -1.9 dB (-5 to 1 dB). The 95% limits of agreement were fairly narrow (-8 to 2 dB) across the 6 Garway-Heath sectors. Most participants preferred to perform GV (68.2%) if required to repeat perimetry compared with HFA (20.6%, P<0.001). CONCLUSIONS: There was fairly good agreement between the threshold sensitivities of GV and HFA. GV was also preferred by most patients and could potentially supplement HFA as a portable or home perimeter.

InstaBP: Cuff-less Blood Pressure Monitoring on Smartphone using Single PPG Sensor.

Cuff-less Blood Pressure (BP) monitoring has gained interest of the research community in recent years, due to its importance in continuous and non-invasive monitoring of BP for early detection of hypertension, thereby reducing mortality. Several approaches that involve photoplethysmography (PPG) and Pulse Transit Time (PTT) have been explored with promising results; however the requirement of two sensors makes them obtrusive for continuous use. Single PPG sensor approaches using machine learning have also been attempted, but there are certain deficiencies in these methods as they go for a one-size-fits-all approach. In this work, we develop an ensemble of BP prediction models based on demographic and physiological partitioning. Also, we incorporate a set of unique PPG features into our models, which results in test accuracies of 5 mmHg Mean Absolute Error (MAE) for Diastolic BP, and 6.9 mmHg MAE for Systolic BP. Given our marked improvement over ubiquitous models (18% for Diastolic BP and 11.5% for Systolic BP), this approach opens up avenues where single PPG sensor based methods can predict BP with a high degree of accuracy. This is a big step towards developing continuous BP monitoring systems, and can help in better management of cardiac health.

Thalamic abnormalities in children with continuous spike-wave during slow-wave sleep: An F-18-fluorodeoxyglucose positron emission tomography perspective.

OBJECTIVE: Thalamic injury has been implicated in the development of continuous spike-wave during slow-wave sleep (CSWS) in children with epilepsy. We studied thalamic abnormalities in children with CSWS using F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. METHODS: Twenty-three patients (12 male; mean age 9 years) with CSWS and normal thalami on brain magnetic resonance imaging (MRI) underwent FDG-PET. Thalamic glucose metabolism, represented by standardized uptake value normalized to whole brain (nSUV, RT for right thalamus and LT for left thalamus), and its asymmetry--absolute asymmetry index (AAI): ¦(RT-LT)¦*100/[(RT+LT)/2]--was calculated. These values were compared with those from 10 normal healthy controls (five female; mean age 11.1 years). RESULTS: Thalamic glucose metabolism was abnormal in 18 patients (78.3%). Thalamic nSUV was decreased (n = 6) or increased (n = 1) bilaterally in seven children without any asymmetry. Abnormal thalamic symmetry [AAI = 3.7-31.5% (0.8-3.3% in controls)] was seen in 11 children. Of these, six children had a unilateral thalamic metabolic abnormality (increased metabolism, n = 3 and decreased metabolism, n = 3), whereas 5 of 14 children had abnormal asymmetry index with bilaterally normal (n = 4) or increased (n = 1) thalamic metabolism. No clear association of thalamic metabolic abnormalities was seen with the stage of evolution of CSWS (prodromal, acute, or residual) or with the cortical FDG abnormalities. SIGNIFICANCE: Functional thalamic abnormalities, both unilateral and bilateral, are frequently seen in patients with CSWS. FDG-PET is a sensitive and quantifiable modality to detect these changes.

Cuff-less PPG based continuous blood pressure monitoring: a smartphone based approach.

Cuff-less estimation of systolic (SBP) and diastolic (DBP) blood pressure is an efficient approach for non-invasive and continuous monitoring of an individual's vitals. Although pulse transit time (PTT) based approaches have been successful in estimating the systolic and diastolic blood pressures to a reasonable degree of accuracy, there is still scope for improvement in terms of accuracies. Moreover, PTT approach requires data from sensors placed at two different locations along with individual calibration of physiological parameters for deriving correct estimation of systolic and diastolic blood pressure (BP) and hence is not suitable for smartphone deployment. Heart Rate Variability is one of the extensively used non-invasive parameters to assess cardiovascular autonomic nervous system and is known to be associated with SBP and DBP indirectly. In this work, we propose a novel method to extract a comprehensive set of features by combining PPG signal based and Heart Rate Variability (HRV) related features using a single PPG sensor. Further, these features are fed into a DBP feedback based combinatorial neural network model to arrive at a common weighted average output of DBP and subsequently SBP. Our results show that using this current approach, an accuracy of ±6.8 mmHg for SBP and ±4.7 mmHg for DBP is achievable on 1,750,000 pulses extracted from a public database (comprising 3000 people). Since most of the smartphones are now equipped with PPG sensor, a mobile based cuff-less BP estimation will enable the user to monitor their BP as a vital parameter on demand. This will open new avenues towards development of pervasive and continuous BP monitoring systems leading to an early detection and prevention of cardiovascular diseases.

StayFit: a wearable application for Gym based power training.

Comprehensive fitness training involves both cardiorespiratory and power components. Often power/muscle strength training is confused with cardiorespiratory endurance training. However, each of them target different physiological aspects of fitness. Although, wearable based fitness trackers designed towards cardiorespiratory endurance training are available in the market, a dedicated wearable based fitness application designed for power training/tracking is still not readily available to fitness enthusiasts. With growing usage of wearable technology to manage and track personal health, it is imperative to develop health/fitness applications for wearables. A wearable based application for power training will allow the user to track build-up of muscle strength unobtrusively over a period of time. This work provides a framework and design for automatic detection, counting repetitions of strength training Gym exercises (covering all the major muscle groups), estimate personalized calories spent in each session and track power on a standalone Gear watch (both analysis and display including User Experience(UX) design). Our proposed method detects activity with ~96% sensitivity and ~96% specificity on an average and count repetitions with an overall accuracy of >95% using motion sensor data (accelerometer, gyroscope) for eight major Gym exercises. Additionally, using heart rate sensor data we have provided a mechanism to individually track the power/muscle strength of a person. This work will give further impetus towards developing wearable based systems for personalized fitness tracking and training. This will also give an option for wearable users to address both the crucial aspects of fitness (cardiorespiratory and muscle strength).

Remote health monitoring system for detecting cardiac disorders.

Remote health monitoring system with clinical decision support system as a key component could potentially quicken the response of medical specialists to critical health emergencies experienced by their patients. A monitoring system, specifically designed for cardiac care with electrocardiogram (ECG) signal analysis as the core diagnostic technique, could play a vital role in early detection of a wide range of cardiac ailments, from a simple arrhythmia to life threatening conditions such as myocardial infarction. The system that the authors have developed consists of three major components, namely, (a) mobile gateway, deployed on patient's mobile device, that receives 12-lead ECG signals from any ECG sensor, (b) remote server component that hosts algorithms for accurate annotation and analysis of the ECG signal and (c) point of care device of the doctor to receive a diagnostic report from the server based on the analysis of ECG signals. In the present study, their focus has been toward developing a system capable of detecting critical cardiac events well in advance using an advanced remote monitoring system. A system of this kind is expected to have applications ranging from tracking wellness/fitness to detection of symptoms leading to fatal cardiac events.

Quantifiable fitness tracking using wearable devices.

Monitoring health and fitness is emerging as an important benefit that smartphone users could expect from their mobile devices today. Rule of thumb calorie tracking and recommendation based on selective activity monitoring is widely available today, as both on-device and server based solutions. What is surprisingly not available to the users is a simple application geared towards quantitative fitness tracking. Such an application potentially can be a direct indicator of one's cardio-vascular performance and associated long term health risks. Since wearable devices with various inbuilt sensors like accelerometer, gyroscope, SPO2 and heart rate are increasingly becoming available, it is vital that the enormous data coming from these sensors be used to perform analytics to uncover hidden health and fitness associated facts. A continuous estimation of fitness level employing these wearable devices can potentially help users in setting personalized short and long-term exercise goals leading to positive impact on one's overall health. The present work describes a step in this direction. This work involves an unobtrusive method to track an individual's physical activity seamlessly, estimate calorie consumption during a day by mapping the activity to the calories spent and assess fitness level using heart rate data from wearable sensors. We employ a heart rate based parameter called Endurance to quantitatively estimate cardio-respiratory fitness of a person. This opens up avenues for personalization and adaptiveness by dynamically using individual's personal fitness data towards building robust modeling based on analytical principles.

Assessment of brain damage and plasticity in the visual system due to early occipital lesion: comparison of FDG-PET with diffusion MRI tractography.

PURPOSE: To determine the relation between glucose metabolic changes of the primary visual cortex, structural abnormalities of the corresponding visual tracts, and visual symptoms in children with Sturge-Weber syndrome (SWS). MATERIALS AND METHODS: In 10 children with unilateral SWS (ages 1.5-5.5 years), a region-of-interest analysis was applied in the bilateral medial occipital cortex on positron emission tomography (PET) and used to track diffusion-weighted imaging (DWI) streamlines corresponding to the central visual pathway. Normalized streamline volumes of individual SWS patients were compared with values from age-matched control groups as well as correlated with normalized glucose uptakes and visual field deficit. RESULTS: Lower glucose uptake and lower corresponding streamline volumes were detected in the affected occipital lobe in 9/10 patients, as compared to the contralateral side. Seven of these 9 patients had visual field deficit and normal or decreased streamline volumes on the unaffected side. The two other children had no visual symptoms and showed high contralateral visual streamline volumes. There was a positive correlation between the normalized ratios on DWI and PET, indicating that lower glucose metabolism was associated with lower streamline volume in the affected hemisphere (R = 0.70, P = 0.024). CONCLUSION: We demonstrated that 18F-flurodeoxyglucose (FDG)-PET combined with DWI tractography can detect both brain damage on the side of the lesion and contralateral plasticity in children with early occipital lesions.

In vivo detection of reduced Purkinje cell fibers with diffusion MRI tractography in children with autistic spectrum disorders.

Postmortem neuropathology studies report reduced number and size of Purkinje cells (PC) in a majority of cerebellar specimens from persons diagnosed with autism spectrum disorders (ASD). We used diffusion weighted MRI tractography to investigate whether structural changes associated with reduced number and size of PC, could be detected in vivo by measuring streamlines connecting the posterior-lateral region of the cerebellar cortex to the dentate nucleus using an independent component analysis with a ball and stick model. Seed regions were identified in the cerebellar cortex, and streamlines were identified to two sorting regions, the dorsal dentate nucleus (DDN) and the ventral dentate nucleus (VDN), and probability of connection and measures of directional coherence for these streamlines were calculated. Tractography was performed in 14 typically developing children (TD) and 15 children with diagnoses of ASD. Decreased numbers of streamlines were found in the children with ASD in the pathway connecting cerebellar cortex to the right VDN (p-value = 0.015). Reduced fractional anisotropy (FA) values were observed in pathways connecting the cerebellar cortex to the right DDN (p-value = 0.008), the right VDN (p-value = 0.010) and left VDN (p-value = 0.020) in children with ASD compared to the TD group. In an analysis of single subjects, reduced FA in the pathway connecting cerebellar cortex to the right VDN was found in 73% of the children in the ASD group using a threshold of 3 standard errors of the TD group. The detection of diffusion changes in cerebellum may provide an in vivo biomarker of Purkinje cell pathology in children with ASD.

SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism.

BACKGROUND: Genetic mutations play a crucial role in the etiology of cryptogenic infantile spasms, but the cause is still unknown in a significant proportion of patients. Whole exome sequencing technology shows great promise in identifying genetic causes of infantile spasms. METHODS: In this study whole exome sequencing was performed with 2-deoxy-2-((18)F)fluoro-d-glucose positron emission tomography scan of an infant boy with infantile spasms. Exome sequencing was also performed in the parents to identify any de novo mutations. RESULTS: The positron emission tomography scan showed a pattern of bilateral symmetric temporal lobe glucose hypometabolism. A total of 8171 nonsynonymous variants were identified in the child. Despite the large number of nonsynonymous variants, there was only a single de novo missense mutation in SCN2A in the child (NCBI hg19 assembly, position: Chr2:166234116, K1422E). Subsequent Sanger sequencing confirmed the de novo status of this variant. This mutation has never been reported in 6500 individuals of the exome variant server database. Similarly, this variant is not reported in the Online Mendelian Inheritance in Man Database or the Human Gene Mutation Database. It has previously been shown that SCN2A mutations are associated with hippocampal hyperexcitability. Therefore, this study indicates that infantile spasms and bitemporal hypometabolism in this patient might have been caused by hippocampal hyperexcitability due to SCN2A mutation. CONCLUSIONS: The simultaneous presence of an SCN2A mutation and bitemporal hypometabolism in this patient with infantile spasms suggests a plausible hippocampal origin. However, additional mechanistic and clinical studies are required to validate this link.

Automatic detection of primary motor areas using diffusion MRI tractography: comparison with functional MRI and electrical stimulation mapping.

PURPOSE: As an alternative tool to identify cortical motor areas for planning surgical resection in children with focal epilepsy, the present study proposed a maximum a posteriori probability (MAP) classification of corticospinal tract (CST) visualized by diffusion MR tractography. METHODS: Diffusion-weighted imaging (DWI) was performed in 17 normally developing children and 20 children with focal epilepsy. An independent component analysis tractography combined with ball-stick model was performed to identify unique CST pathways originating from mouth/lip, finger, and leg areas determined by functional magnetic resonance imaging (fMRI) in healthy children and electrical stimulation mapping (ESM) in children with epilepsy. Group analyses were performed to construct stereotaxic probability maps of primary motor pathways connecting precentral gyrus and posterior limb of internal capsule, and then utilized to design a novel MAP classifier that can sort individual CST fibers associated with three classes of interest: mouth/lip, fingers, and leg. A systematic leave-one-out approach was applied to train an optimal classifier. A match was considered to occur if classified fibers contacted or surrounded true areas localized by fMRI and ESM. KEY FINDINGS: It was found that the DWI-MAP provided high accuracy for the CST fibers terminating in proximity to the localization of fMRI/ESM: 78%/77% for mouth/lip, 77%/76% for fingers, 78%/86% for leg (contact), and 93%/89% for mouth/lip, 91%/89% for fingers, and 92%/88% for leg (surrounded within 2 cm). SIGNIFICANCE: This study provides preliminary evidence that in the absence of fMRI and ESM data, the DWI-MAP approach can effectively retrieve the locations of cortical motor areas and underlying CST courses for planning epilepsy surgery.

Infantile spasms are associated with abnormal copy number variations.

The authors tested the hypothesis that de novo copy number variations (CNVs) implicated in known genomic disorders ("pathogenic CNVs") are significant predisposing factors of infantile spasms. The authors performed a genome-wide analysis of single-nucleotide polymorphism genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms. A rare, large (4.8 Mb) de novo duplication was detected in the 15q11-13 region of 1 patient. In addition, 3 known pathogenic CNVs (present in the patient as well as 1 of the parents) were detected in total. In 1 patient, a known pathogenic deletion was detected in the region of 2q32.3. Similarly, in 1 other patient, 2 known pathogenic deletions in the regions of 16p11.2 and Xp22.13 (containing CDKL5) were detected. These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes.

Altered white matter structure of the dentatorubrothalamic pathway in children with autistic spectrum disorders.

Neuropathological studies have demonstrated decreased Purkinje cells in cerebellar cortex and changes in the dentate nucleus of the cerebellum, the projection target for the Purkinje cells, in autistic spectrum disorders (ASD). The dentatorubrothalamic tract is formed by efferents from the dentate nucleus projecting toward the red nucleus with axon collaterals to this nucleus and continuing to innervate the ventral lateral and ventral anterior nuclei of the thalamus. In the current study, we assessed whether the dentatorubrothalamic tract is altered in ASD using Q-ball imaging (QBI). The QBI tractography was performed in 13 children with high functioning ASD (HFA), 11 children with low functioning ASD (LFA), and 14 typically developing children (TD). Regions of interest in dentate nucleus and red nucleus in both hemispheres were objectively placed to sort bilateral dorsal-rostral (DR), dorsal-caudal (DC), ventral-rostral (VR), and ventral-caudal (VC) portions of the dentatorubrothalamic pathway. Group differences in fractional anisotropy (FA), axial diffusivity, radial diffusivity, and fiber volume of individual pathways were analyzed. Significantly reduced FA was found in children with LFA and HFA, compared to the TD group in tracts originating in all four subdivisions of the right dentate nucleus. Tract-based morphometry (TBM) analysis demonstrated significant reductions of FA in caudal midbrain (p<0.0001), dorsal-caudal dentate (p=0.0013), and ventral-caudal dentate (p=0.0061) on the right in the LFA group. The FA values in TBM segments of right VR and VC pathways were significantly correlated with communication skills in the combined HFA/LFA group, while there was a significant correlation found between TBM segments of right DR pathway and daily living skills (r=0.76; p=0.004). Decreased white matter integrity in dorsal portions of the dentatorubrothalamic tract may be related to motor features in ASD, while changes in the ventral portions are related more to communication behavior.

Relationship between aberrant brain connectivity and clinical features in Angelman Syndrome: a new method using tract based spatial statistics of DTI color-coded orientation maps.

AIM: In order to relate brain structural abnormalities to clinical features of Angelman Syndrome (AS), we determined the locations of abnormal regional white matter architecture in AS children using a sensitive and objective whole brain approach to analyze diffusion tensor imaging (DTI) color-coded orientation maps. METHODS: Using tract based spatial statistics (TBSS) of DTI color-coded orientation maps, the fraction of fibers oriented in the anteroposterior (AP), mediolateral (ML) and superioinferior (SI) directions were determined in whole brain white matter of 7 children with AS (mean age: 70±25.78 months, 5 males) and 7 children with typical development (TD, mean age: 79.8±17.25 months, 4 males). TBSS of FA map was also performed for comparison. RESULTS: Children with AS had a significantly lower AP component than the TD group in 9 clusters (3 bilateral and 3 unilateral). Bilateral clusters were located in inferior fronto-occipital fasciculus, anterior thalamic radiation and arcuate fasciculus regions. Unilateral clusters involved left brainstem, left cingulum and right uncinate regions. Similarly, children with AS had significantly lower ML component than the TD group in 4 clusters (2 in corpus callosum and 2 unilateral clusters). Unilateral clusters were located in the left cingulum and left anterior thalamic radiation regions. SI component was lower in children with AS in two clusters compared to TD (corticospinal tract and corpus callosum). FA map clusters mostly corresponded with component clusters. INTERPRETATION: Children with AS have a global impairment of white matter integrity including AP, ML and SI components in whole brain suggesting a potential underlying error with axon guidance mechanisms during brain development possibly due to loss of UBE3A gene expression. Some of this aberrant connectivity can be related to the clinical features of AS.

New radiosynthesis of 2-deoxy-2-[(18)F]fluoroacetamido-D-glucopyranose and its evaluation as a bacterial infections imaging agent.

INTRODUCTION: The diagnosis of infection and the ability to distinguish bacterial infection from nonbacterial inflammation by positron emission tomography (PET) have gained interest in recent years, but still few specific radiopharmaceuticals are available for use. In this study, we developed a new radiosynthesis method of 2-deoxy-2-[(18)F]fluoroacetamido-d-glucopyranose ([(18)F]FAG) by applying microwave irradiation and demonstrated that [(18)F]FAG could be a potential radiopharmaceutical to distinguish bacterial infection from nonbacterial inflammation. METHODS: 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose was used as precursor, and labeling was performed under microwave irradiation conditions followed by alkaline hydrolysis and high-performance liquid chromatography (HPLC) purification. In vitro uptake of [(18)F]FAG by Escherichia coli was performed. Tissue biodistribution of [(18)F]FAG was performed in mice. Moreover, PET imaging acquisition of E. coli infection and nonbacterial inflammation models was performed in rats. Tissue radiotracer-accumulated sites were analyzed by hematoxylin and eosin staining and anti-E.coli immunostaining. RESULTS: The radiosynthesis of [(18)F]FAG was achieved with microwave irradiation, and the radiochemical yield was 9.7%±2.8% end of bombardment (EOB); the radiochemical purity was more than 98%, and the total synthesis time was 62 min. Compared with control group, in vitro uptake of [(18)F]FAG by E. coli was significantly decrease in inhibition group (P<.05). Biodistribution studies in mice showed rapid clearance of [(18)F]FAG from the animal body. [(18)F]FAG clearly visualized the infection areas but not nonbacterial inflammation areas in PET studies. Quantitative analysis revealed that the uptake of [(18)F]FAG into infection areas was significantly higher than that of [(18)F]FAG into inflammation areas (P<.05). Histological analysis demonstrated the presence of bacterial cells at the sites of accumulation of [(18)F]FAG. CONCLUSIONS: Using 1,3,4,6-tetra-O-acetyl-2-deoxy-2-bromoacetamido-d-glucopyranose as a precursor, the new radiosynthesis method of [(18)F]FAG was achieved in fewer steps and with a shorter synthesis time than previously reported. Furthermore, [(18)F]FAG was able to distinguish bacterial infection from nonbacterial inflammation.